Explore the vast range of titles available.

Type 1 diabetes mellitus (T1D) can occur at any age, with a peak in incidence around puberty. Classification between T1D and type 2 diabetes becomes more challenging with increasing age of onset of T1D over time develops in genetically predisposed individuals. The main susceptibility is conferred with human leukocyte antigen (HLA) genes. Some of the geographic variation in incidence and familial aggregation is explained by differences in HLA haplotypes. In many populations, the incidence is somewhat higher in males than in females, and a 1.3- to 2.0-fold male excess in incidence after about 15 years of age exists in most populations. The incidence of childhood-onset T1D varies markedly among countries. East Asian and native American populations have low incidences (approximately 0.1–8 per 100 000/year), while the highest rates are found in Finland (>60 per 100 000/year), Sardinia (40 per 100 000/year), and Sweden (47 per 100 000/year). The risk is highest in European-derived populations. About 10 %–20 % of newly diagnosed childhood cases of T1D have an affected first-degree relative. Those with an affected sibling or parent have a cumulative risk of 3 %–7 % up to about 20 years of age, as compared with <1 % in the general population. The cumulative incidence among the monozygotic co-twins of persons with T1D is less than 50 %. Thus, the majority of genetically predisposed people do not develop T1D. Studies assessing temporal trends have shown that the incidence of childhood-onset T1D has increased in all parts of the world. The average relative increase is 3 %–4 % per calendar year. For instance, in Finland, the incidence today is 5 times higher than 60 years ago. At the same time, the age at onset of T1D in children has become younger. It is strongly believed that nongenetic factors are important for the development of T1D and its increase, but the causative evidence is missing. The causes for this increasing trend and current epidemic still remain unknown.

Atherosclerosis imposes a heavy burden on cardiovascular health due to its indispensable role in the pathogenesis of cardiovascular disease (CVD) such as coronary artery disease and heart failure. Ample clinical and experimental evidence has corroborated the vital role of inflammation in the pathophysiology of atherosclerosis. Hence, the demand for preclinical research into atherosclerotic inflammation is on the horizon. Indeed, the acquisition of an in-depth knowledge of the molecular and cellular mechanisms of inflammation in atherosclerosis should allow us to identify novel therapeutic targets with translational merits. In this review, we aimed to critically discuss and speculate on the recently identified molecular and cellular mechanisms of inflammation in atherosclerosis. Moreover, we delineated various signaling cascades and proinflammatory responses in macrophages and other leukocytes that promote plaque inflammation and atherosclerosis. In the end, we highlighted potential therapeutic targets, the pros and cons of current interventions, as well as anti-inflammatory and atheroprotective mechanisms.

Obesity is the most important risk factor for obstructive sleep apnea (OSA). However, although included in clinical guidelines, no randomized controlled studies have been performed on the effects of weight reduction on mild OSA. The aim of this prospective, randomized controlled parallel-group 1-year follow-up study was to determine whether a very low calorie diet (VLCD) with supervised lifestyle counseling could be an effective treatment for adults with mild OSA. Seventy-two consecutive overweight patients (body mass index, 28-40) with mild OSA were recruited. The intervention group (n = 35) completed the VLCD program with supervised lifestyle modification, and the control group (n = 37) received routine lifestyle counseling. The apnea-hypopnea index (AHI) was the main objectively measured outcome variable. Change in symptoms and the 15D-Quality of Life tool were used as subjective measurements. The lifestyle intervention was found to effectively reduce body weight (-10.7 +/- 6.5 kg; body mass index, -3.5 +/- 2.1 [mean +/- SD]). There was a statistically significant difference in the mean change in AHI between the study groups (P = 0.017). The adjusted odds ratio for having mild OSA was markedly lowered (odds ratio, 0.24 [95% confidence interval, 0.08-0.72]; P = 0.011) in the intervention group. All common symptoms related to OSA, and some features of 15D-Quality of Life improved after the lifestyle intervention. Changes in AHI were strongly associated with changes in weight and waist circumference. VLCD combined with active lifestyle counseling resulting in marked weight reduction is a feasible and effective treatment for the majority of patients with mild OSA, and the achieved beneficial outcomes are maintained at 1-year follow-up.

Functional foods contain biologically active ingredients associated with physiological health benefits for preventing and managing chronic diseases, such as type 2 diabetes mellitus (T2DM). A regular consumption of functional foods may be associated with enhanced anti-oxidant, anti-inflammatory, insulin sensitivity, and anti-cholesterol functions, which are considered integral to prevent and manage T2DM. Components of the Mediterranean diet (MD)—such as fruits, vegetables, oily fish, olive oil, and tree nuts—serve as a model for functional foods based on their natural contents of nutraceuticals, including polyphenols, terpenoids, flavonoids, alkaloids, sterols, pigments, and unsaturated fatty acids. Polyphenols within MD and polyphenol-rich herbs—such as coffee, green tea, black tea, and yerba maté—have shown clinically-meaningful benefits on metabolic and microvascular activities, cholesterol and fasting glucose lowering, and anti-inflammation and anti-oxidation in high-risk and T2DM patients. However, combining exercise with functional food consumption can trigger and augment several metabolic and cardiovascular protective benefits, but it is under-investigated in people with T2DM and bariatric surgery patients. Detecting functional food benefits can now rely on an “omics” biological profiling of individuals’ molecular, genetics, transcriptomics, proteomics, and metabolomics, but is under-investigated in multi-component interventions. A personalized approach for preventing and managing T2DM should consider biological and behavioral models, and embed nutrition education as part of lifestyle diabetes prevention studies. Functional foods may provide additional benefits in such an approach.

Finland has the highest incidence of type 1 diabetes worldwide, reaching 40 per 100 000 people per year in the 1990s. Our aim was to assess the temporal trend in type 1 diabetes incidence since 2000 in Finnish children aged younger than 15 years and to predict the number of cases of type 1 diabetes in the future. Children with newly diagnosed type 1 diabetes in Finland who were listed on the National Public Health Institute diabetes register, Central Drug Register, and Hospital Discharge Register in 1980–2005 were included in a cohort study. We excluded patients with type 2 diabetes and diabetes occurring secondary to other conditions, such as steroid use, Down's syndrome, and congenital malformations of pancreas. 10 737 children—5816 boys and 4921 girls—were diagnosed with type 1 diabetes before 15 years of age during 1980–2005. The average age-standardised incidence was 42·9 per 100 000 per year (95% CI 42·6–44·3) during this period, increasing from 31·4 per 100 000 per year in 1980 to 64·2 per 100 000 per year in 2005. The age-specific rates per 100 000 per year were 31·0, 50·5, and 50·6 at ages 0–4 years, 5–9 years, and 10–14-years, respectively. We noted a significant non-linear component to the time trend (p<0·0003). In children aged 0–4 years, the increase was largest, at 4·7% more affected every year. The overall boy-to-girl ratio of incidence was 1·1; at the age of 13 years, it was 1·7 (1·4–2·0). The predicted cumulative number of new cases with type 1 diabetes before 15 years of age between 2006 and 2020 was about 10 800. The incidence of type 1 diabetes in Finnish children is increasing even faster than before. The number of new cases diagnosed at or before 14 years of age will double in the next 15 years and the age of onset will be younger (0–4 years). Academy of Finland, Sigrid Jusélius Foundation, Juvenile Diabetes Research Foundation.

About 10% of people older than 70 years of age carry one or more mutations in their hematopoietic cells, and these persons have a higher relative risk of a hematologic cancer (by a factor of 11) and of death from cardiovascular disease (by a factor of 2.0 to 2.6). Cancer is thought to arise through the stepwise acquisition of genetic or epigenetic changes that transform a normal cell. 1 Hence, the existence of a premalignant state bearing only the initiating lesions may be detectable in some persons who have no other signs of disease. For example, multiple myeloma is frequently preceded by monoclonal gammopathy of unknown significance, 2 and chronic lymphocytic leukemia is commonly preceded by monoclonal B-cell lymphocytosis. 3 Several lines of evidence have suggested that clonal hematopoiesis resulting from an expansion of cells that harbor an initiating driver mutation might be an aspect of the aging hematopoietic system. Clonal hematopoiesis . . .

Cellular senescence is a process in which the cell cycle becomes permanently arrested, thereby inhibiting cell division, proliferation and growth. Various cellular stresses, such as DNA damage, telomere shortening and oxidative stress, can trigger cellular senescence. Physiologically, cellular senescence contributes to tissue development, repair and critical biological processes such as embryogenesis, whereas, pathologically, it plays a key role in diverse disease subsets. To this end, elucidating the underlying mechanisms and molecular regulation of senescence is crucial. Here, in this Review, we explore recent key findings on cellular senescence in experimental and human disease models, focusing on its molecular mechanisms, regulation and future research directions to advance the field and facilitate therapeutic translation. Cellular senescence mechanisms impacting health and disease Cellular senescence is a natural process in which cells stop dividing in response to stress, such as DNA damage. However, it can also contribute to diseases such as idiopathic pulmonary fibrosis (IPF), a lung condition with unknown causes. Researchers found that a protein called YTHDC1 can delay cellular senescence and reduce lung fibrosis by improving DNA repair in cells. They studied this in mice and found that increasing YTHDC1 levels helped to repair DNA and reduced fibrosis. The study used experimental methods to overexpress YTHDC1 in mouse lung cells, showing its potential to reverse senescence. The results suggest that targeting YTHDC1 could be a new way to treat IPF. However, more research is needed to confirm these findings and explore their safety in humans. In conclusion, understanding cellular senescence’s role in diseases such as IPF could lead to new treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Very few studies have explored the patterns of cardiovascular health (CVH) metrics in midlife and late life in relation to risk of dementia. We examined the associations of composite CVH metrics from midlife to late life with risk of incident dementia. This cohort study included 1,449 participants from the Finnish Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study, who were followed from midlife (baseline from1972 to 1987; mean age 50.4 years; 62.1% female) to late life (1998), and then 744 dementia-free survivors were followed further into late life (2005 to 2008). We defined and scored global CVH metrics based on 6 of the 7 components (i.e., smoking, physical activity, and body mass index [BMI] as behavioral CVH metrics; fasting plasma glucose, total cholesterol, and blood pressure as biological CVH metrics) following the modified American Heart Association (AHA)'s recommendations. Then, the composite global, behavioral, and biological CVH metrics were categorized into poor, intermediate, and ideal levels. Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Data were analyzed with Cox proportional hazards and the Fine and Gray competing risk regression models. During the follow-up examinations, dementia was diagnosed in 61 persons in 1998 and additional 47 persons in 2005 to 2008. The fully adjusted hazard ratio (HR) of dementia was 0.71 (95% confidence interval [CI]: 0.43, 1.16; p = 0.174) and 0.52 (0.29, 0.93; p = 0.027) for midlife intermediate and ideal levels (versus poor level) of global CVH metrics, respectively; the corresponding figures for late-life global CVH metrics were 0.60 (0.22, 1.69; p = 0.338) and 0.91 (0.34, 2.41; p = 0.850). Compared with poor global CVH metrics in both midlife and late life, the fully adjusted HR of dementia was 0.25 (95% CI: 0.08, 0.86; p = 0.028) for people with intermediate global CVH metrics in both midlife and late life and 0.14 (0.02, 0.76; p = 0.024) for those with midlife ideal and late-life intermediate global CVH metrics. Having an intermediate or ideal level of behavioral CVH in both midlife and late life (versus poor level in both midlife and late life) was significantly associated with a lower dementia risk (HR range: 0.03 to 0.26; p < 0.05), whereas people with midlife intermediate and late-life ideal biological CVH metrics had a significantly increased risk of dementia (p = 0.031). Major limitations of this study include the lack of data on diet and midlife plasma glucose, high rate of attrition, as well as the limited power for certain subgroup analyses. In this study, we observed that having the ideal CVH metrics, and ideal behavioral CVH metrics in particular, from midlife onwards is associated with a reduced risk of dementia as compared with people having poor CVH metrics. Maintaining life-long health behaviors may be crucial to reduce late-life risk of dementia.

Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia; however, the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting, and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence. The Hypertension in the Very Elderly trial (HYVET) was designed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function. Patients with hypertension (systolic pressure 160–200 mm Hg; diastolic pressure <110 mm Hg) who were aged 80 years or older were enrolled in this double-blind, placebo-controlled trial. Participants were randomly assigned to receive 1·5 mg slow release indapamide, with the option of 2–4 mg perindopril, or placebo. The target systolic blood pressure was 150 mm Hg; the target diastolic blood pressure was 80 mm Hg. Participants had no clinical diagnosis of dementia at baseline, and cognitive function was assessed at baseline and annually with the mini-mental state examination (MMSE). Possible cases of incident dementia (a fall in the MMSE score to <24 points or a drop of three points in 1 year) were assessed by standard diagnostic criteria and expert review. The trial was stopped in 2007 at the second interim analysis after treatment resulted in a reduction in stroke and total mortality. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00122811. 3336 HYVET participants had at least one follow-up assessment (mean 2·2 years) and were included: 1687 participants were randomly assigned to the treatment group and 1649 to the placebo group. Only five reports of adverse effects were attributed to the medication: three in the placebo group and two in the treatment group. The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic −15 mm Hg, p<0·0001; and diastolic −5·9 mm Hg, p<0·0001. There were 263 incident cases of dementia. The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group. There was no significant difference between treatment and placebo groups (hazard ratio [HR] 0·86, 95% CI 0·67–1·09); however, when these data were combined in a meta-analysis with other placebo-controlled trials of antihypertensive treatment, the combined risk ratio favoured treatment (HR 0·87, 0·76–1·00, p=0·045). Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia. This negative finding might have been due to the short follow-up, owing to the early termination of the trial, or the modest effect of treatment. Nevertheless, the HYVET findings, when included in a meta-analysis, might support antihypertensive treatment to reduce incident dementia. The British Heart Foundation; the Institute de Recherches Internationales Servier.

There is concern about an emerging diabetes epidemic in Turkey. We aimed to determine the prevalence of diagnosed and undiagnosed diabetes, prediabetes and their 12-year trends and to identify risk factors for diabetes in the adult Turkish population. A cross-sectional, population-based survey, 'TURDEP-II' included 26,499 randomly sampled adults aged ≥ 20 years (response rate: 87 %). Fasting glucose and biochemical parameters were measured in all; then a OGTT was performed to identify diabetes and prediabetes in eligible participants. The prevalence of diabetes was 16.5 % (new 7.5 %), translating to 6.5 million adults with diabetes in Turkey. It was higher in women than men (p = 0.008). The age-standardized prevalence to the TURDEP-I population (performed in 1997–98) was 13.7 % (if same diagnostic definition was applied diabetes prevalence is calculated 11.4 %). The prevalence of isolated-IFG and impaired glucose tolerance (IGT), and combined prediabetes was 14.7, 7.9, and 8.2 %, respectively; and that of obesity 36 % and hypertension 31.4 %. Compared to TURDEP-I; the rate of increase for diabetes: 90 %, IGT: 106 %, obesity: 40 % and central obesity: 35 %, but hypertension decreased by 11 % during the last 12 years. In women age, waist, body mass index (BMI), hypertension, low education, and living environment; in men age, BMI, and hypertension were independently associated with an increased prevalence of diabetes. In women current smoking, and in men being single were associated with a reduced risk. These results from one of the largest nationally representative surveys carried out so far show that diabetes has rapidly become a major public health challenge in Turkey. The figures are alarming and underscore the urgent need for national programs to prevent diabetes, to manage the illness and thus prevent complications.